It is ironic that decongestant, antihistamine and cough ("cough/cold") medications are among the most commonly used drugs during pregnancy, yet their safety with respect to birth defects is not established. Given the wide use of these drugs, even a small increase in the risk of birth defects may have considerable clinical and public health implications. Thus, we will evaluate the association between in utero exposure to these drugs and 1) specific major malformations previously hypothesized to be associated with each of them, and 2) other specific major malformations that occur commonly in the general population. These goals can be efficiently achieved by taking advantage of data available through a large ongoing multicenter case-control surveillance program of birth defects in North America, the Slone Epidemiology Center Birth Defects Study (BDS). The BDS has involved over 100 birth and tertiary hospitals in the greater metropolitan areas of Boston, Philadelphia, Toronto, San Diego, and selected regions in Iowa, as well as birth defects registries in Massachusetts and New York State, and has, since 1976, interviewed more than 35,000 mothers of babies with and without birth defects. The BDS identifies infants with a wide range of malformations (ICD codes 740.0-759.9) and a sample of non-malformed infants within 5 months after birth, and study nurses interview mothers within 6 months of delivery about demographic, reproductive, and medical factors;cigarette smoking and alcohol consumption;dietary intake;and details about use of a wide range of medications, including prescription over-the-counter drugs. The study has successfully identified both risks and safety of selected over-the-counter medications-findings which have been confirmed by others. We propose to first characterize the patterns of use of cough/cold medications during pregnancy and the changes in drug utilization over the study period. We then will estimate the risk of specific birth defects associated with first trimester exposure to specific decongestant, antihistamine and cough medications. Odds ratios and 95 per cent confidence intervals will be calculated using conditional logistic regression models to adjust for potential confounders. Findings from this effort will improve our understanding of risks associated with drugs commonly used by pregnant women, will inform therapeutic guidelines, and will provide leads for further research. PUBLIC HEALTH RELEVANCE: Decongestant, antihistamine and cough medications are among the most commonly used drugs during pregnancy, but the safety of these medications with respect to birth defects is not established. This study will evaluate whether use of these drugs in pregnancy is associated with an increased risk of major birth defects. Findings will improve our understanding of risks associated with these drugs, will help health care providers and pregnant women make informed choices, and will provide leads for further research.